P938: CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE CONSOLIDATION IN MYELOMA PATIENTS WITH A POSITIVE FDG PET/CT AFTER UPFRONT AUTOLOGOUS STEM CELL TRANSPLANTATION: A PHASE II STUDY (CONPET)
Authors: J. N. Nørgaard, N. Abildgaard, A. Lysén, G. Tsykunova, A. J. Vangsted, C. Joao, N. Remen, L. Osnes, J. P. Connelly, M.-E. R. Revheim, F. Schjesvold
Journal: HemaSphere (2022)

Background: [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) positivity after first line treatment with autologous stem cell transplantation (ASCT), is strongly correlated with reduced progression free survival and overall survival (Moreau et al., JCO, 2017). However, FDG PET/CT positive patients who obtain FDG PET/CT negativity after treatment seem to have comparable outcomes to patients who were FDG PET/CT negative at baseline (Davies et al., Haematologica 2018). Aims: Aiming for FDG PET/CT negativity may be an important goal in myeloma treatment. The use of FDG PET/CT positivity as an indication for consolidation therapy after ASCT has not been studied before. We here present the complete data of the primary endpoint, PET/CT negativity after KRd consolidation. Methods: Patients with multiple myeloma who had received standard first line treatment including ASCT and achieved very good partial response (VGPR) or better, were examined by FDG PET/CT. Patients who were FDG PET/CT positive defined by the Italian Myeloma criteria for PET USe (IMPETUS) (Nanni C et al., EJNMMI 2016 and 2018) were included in the treatment phase of the study and were assessed for minimal residual disease (MRD) by Euroflow (sensitivity: 10-5) before treatment. FDG PET/CT examinations were centrally read by two experienced nuclear medicine radiologists. The treatment consisted of four 28-day cycles of KRd (carfilzomib 36 mg/m2 day 1,2,8,9,15 and 16 (except 20 mg/m2 day 1 and 2 first cycle), lenalidomide 25 mg day 1-21 all cycles and dexamethasone 40 mg day 1,8,15 and 22 all cycles). After 4 cycles, FDG PET/CT and Euroflow for MRD were repeated for response evaluation. Both patients with FDG PET/CT negativity and patients with FDG PET/CT positivity at baseline are followed for progression free survival and overall survival. Results: 159 patients were screened with FDG PET/CT. Fifty-three patients of 159 (33%) had a positive FDG PET/CT result. Among FDG PET/CT positive patients, a higher proportion had ISS score III, high-risk cytogenetics and VCd induction was more common (Table 1). Forty-eight patients completed KRd treatment. Sixteen patients (33%) converted into FDG PET/CT negativity. More patients with previous VRd induction than VCd induction converted from FDG PET/CT positive to FDG PET/CT negative (38% vs 20%). No patients stopped treatment due to adverse events. Twenty-seven of 49 (55%) patients with a FDG PET/CT positive result were MRD negative before KRd consolidation. A higher proportion of MRD negative patients vs MRD positive patients before KRd treatment, converted into FDG PET/CT negativity, with 37% vs 28%, respectively. For the proportion of patients that after KRd treatment was both FDG PET/CT negative and MRD negative by EuroFlow, the difference was even higher (37% vs 5% in MRD negative vs MRD positive patients, respectively). In total, the MRD negativity rate increased from 55% to 76% Image:Summary/Conclusion: Before KRd consolidation, 33% of patients in VGPR or better after first line treatment including ASCT were FDG PET/CT positive. High-risk cytogenetics, ISS score III and VCd induction were more common in FDG PET/CT positive patients. After four cycles of KRd, 33% of patients converted from FDG PET/CT positivity to negativity. A higher proportion converted into FDG PET/CT negativity in patients who were MRD negative before KRd treatment, and in patients who had received VRd. KRd consolidation is feasible and converts a clinically significant proportion of FDG PET/CT positive patients to negativity. Patients are followed for PFS and OS.